Method of Increasing Muscle Mass and Strength and Compositions Therefor

ABSTRACT

A method of increasing muscle mass and strength in mammals by orally administering a therapeutically effective amount of phosphatidic acid. The phosphatidic acid is preferably administered as a plurality of doses per day with at least one dose being administered during the anabolic window following exercise. Preferably, the method further includes the cotemporaneous administration of a therapeutically effective amount of creatine, optionally as phosphatidylcreatine. In addition or in the alternative, the method further includes the cotemporaneous administration of a therapeutically effective amount of leucine, optionally as phosphatidylleucine.

BACKGROUND OF THE INVENTION Field of the Invention

The invention relates to methods and compositions for increasing musclemass and strength in mammals. More specifically, the invention relatesto orally ingestible compositions for increasing muscle mass andstrength in mammals to a greater degree than exercise alone wouldprovide.

Description of Related Art

Maintaining one's muscles in a healthy state is critical for one'smetabolism, physical performance, and overall wellbeing. Muscles arecomposed of the contractile proteins myosin and actin; together, theseform myofibrils. Contraction occurs when actin ratchets over the myosin,shortening the length of the myofibrils. Like all proteins, thesecontractile proteins begin with a genetic response, through theribosomal synthetic apparatus. The resulting proteins are incorporatedinto existing myofibrils to increase the size of the muscle, calledmuscular hypertrophy, or to repair the damage that occurs duringcontraction. This system requires adequate nutrition to provide theamino acids that form the protein. In addition, the pathways arecontrolled by activating factors. Muscular hypertrophy is known to beachieved by exercise, especially exercise vigorous enough to reach theanaerobic threshold. Within a short time of commencing such exercise, amammal will achieve measurable mass increase and strength. The increaseddemand has caused the synthetic machinery to be up-regulated. Theactivating factors that may cause the up-regulation in response todemand include the second messenger system which is known to includephospholipases, protein kinases, and the like. Put another way, while itis known that exercise can increase the size and strength of mammalianmuscles, other factors, such as proper nutritional intake, contribute toan increase in mammalian muscle size and strength.

There are a number of commercially available orally ingestiblenutritional supplements advertised for promoting muscle growth. However,there remains a long-felt need to provide an orally ingestiblenutritional supplement that can actively assist in the development andmaintenance of muscular hypertrophy.

SUMMARY OF THE INVENTION

The invention is a method of increasing muscle mass and strength inmammals. The method includes the step of orally administering acomposition comprising a therapeutically effective amount ofphosphatidic acid. In cases where the mammal is human, thetherapeutically effective amount of phosphatidic acid is expected to be0.5-4.0 grams per day. Preferably, the therapeutically effective amountof phosphatidic acid is expected to be approximately 1.0-1.5 grams perday.

The oral administration step further includes the step of dividing thetherapeutically effective amount of phosphatidic acid into a pluralityof doses per day with at least one dose being administered within 1-2hours following an exercise session. Optionally, the oral administrationstep is executed to an exercising subject following exercise during theanabolic window.

Optionally, the method further includes the step of orally administering20-100 grams of protein during the anabolic window, e.g., as food. Theprotein may optionally be a complete protein containing all theessential amino acids, and/or it may be whey, partially hydrolyzedcollagen protein, or the like.

Preferably, the method further includes the cotemporaneousadministration of a therapeutically effective amount of creatine, e.g.,3-20 grams. In one embodiment, the composition includesphosphatidylcreatine.

In addition or in the alternative, the method further includes thecotemporaneous administration of a therapeutically effective amount ofleucine, e.g., 2-5 grams, more preferably about 3 grams of leucine. Inone embodiment, the composition includes phosphatidylleucine.Optionally, the method includes the administration of leucine,isoleucine, and valine in a 2:1:1 ratio, e.g., 4 grams leucine : 2 gramsisoleucine : 2 grams valine.

Other variations and formulations are contemplated.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a schematic depicting various mechanisms of PA formation.

FIG. 2 is a schematic depicting PA activation.

DETAILED DESCRIPTION OF THE INVENTION

Description will now be given of the invention with reference to theattached FIGS. 1-2. It should be understood that these figures areexemplary in nature and in no way serve to limit the scope of theinvention, which is defined by the claims appearing hereinbelow.

The invention is a method of increasing muscle mass and strength inmammals by orally administering a therapeutically effective amount ofphosphatidic acid, as well as a nutritional supplement containing atherapeutically effective amount of phosphatidic acid.

Phosphatidic acid is a known phospholipid that is a constituent of cellmembranes, forming a minor portion of the total phospholipid pool inresting cells. As the smallest of the phospholipids it regularly acts asa precursor to other phospholipids, but also as a second messenger.

FIG. 1 shows several possible mechanisms of PA formation, apart frombrand new creation (i.e., de novo synthesis). Phosphatidic acid (PA) isprimarily synthesized from phosphatidylcholine (PC) by the enzymephospholipase D (PLD). PA can also be synthesized from lysophosphatidicacid (LPA) by the LPA acyltransferase (LPAAT). LPA is primarily derivedfrom glycerol-3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).PA can also be synthesized from diacylglycerol (DAG) by the DAG kinase(DGK). DAG is primarily derived from phosphatidyinositol-4,5-biphosphate(PIP2). The primary enzymes responsible for PA degradation includephospholipase A (PLA), which generates LPA, and PA phosphohydrolase(PAP), which generates DAG. PA can also be degraded to cytidinediphosphate DAG (CDP-DAG) which serves as a precursor for the formationof a variety of lipids. The pathways that regulate PA concentration inresponse to mechanical stimulation have yet to be fully defined.(Hornberger et al, 2006.)

Under normal conditions, PA activation depends on phospholipase D (PLD)enzyme activity, which hydrolyses phosphatidilcholine to PA and choline(Hong, J H et al, 2001). PA then binds the FRB domain of a proteincalled mTOR and activates p70s6k activity, which is one of the keyribosomes of the translation phase of protein synthesis (Fang, Y, 2003).Another study has demonstrated that PA plays a “critical role” in themechanical activation of mTOR signaling (T. A. Hornberger, 2006). Thestudy concluded several points of note. First, an elevation in PAconcentration was sufficient for the activation of mTOR signaling.Second, mechanical stimulation (e.g., substantially anaerobic activitysuch as weight lifting) induced PLD activation, PA accumulation, andmTOR signaling. We theorize that mTOR signaling is at least partlycaused by PA accumulation. Finally, if PLD is blocked, PA accumulationis also blocked, and as a consequence, mTOR signaling is prevented.Given that signaling through mTOR is necessary for mechanically-inducedgrowth of skeletal muscle, and given that an elevation in PA isnecessary for the mechanical activation of mTOR signaling, it has beentheorized that mechanical stimuli induce skeletal muscle growth througha PA-dependent activation of mTOR.

This information suggests that PA is key to the cascade of growthsignals that process following workouts and without it repair and growthpotential is retarded. We theorize that increasing the concentration ofPA via oral administration would amplify this growth signaling cascade.

Another interesting note is that PA binds to and activates p70S6K, evenin the absence of mTOR (Nicholas Lehman et al, 2007). This suggests thatPA can have anabolic potential at other times of day regardless ofwhether one has just exercised or not.

PA-induced activation of mTOR is also independent of a protein calledwortmannin, an enzyme that inhibits mTOR activation by nutrients andgrowth factors. Therefore, while amino acids such as leucine can causeanabolism via mTOR activation, they can be inhibited by wortmannin. PAdoes not suffer this fate (see FIG. 2).

Prophetic doses of PA would be on the order of 1-4 grams per day, morepreferably 1-1.5 grams per day. We theorize that such a dosing rangewould be viable based on similar dosing levels of leucine (which worksthrough mTOR) and phosphatidylserine dosing. We expect that the dosingought to be split into at least two doses per day, with at least onedose following an exercise session before the anabolic window closes(e.g., within 1-2 hours) to help amplify the effects of the workout andthe effect of the post workout meal. Because PA works independently ofthe pathway that leucine works, we expect it will be advantageous toingest the PA supplement with food, as it will complement the action ofleucine or similar amino acids. If the user exercises at night, then itis probably best to ingest the PA supplement upon awakening, with food,and then again in the anabolic window following an exercise session. Asan example, we expect that the post-exercise meal should include 20 to100 grams of protein and/or an amino acid formula during the anabolicwindow. Depending on the source of the PA, e.g., lecithin, it would helpwith the taste and texture of the PA supplement (e.g., in drink mixform). Preferably, the concomitant protein is a complete proteincontaining all the essential amino acids. In addition or in thealternative, the protein is whey or partially hydrolyzed collagenprotein, which would be extremely convenient in the form of a proteinshake as well as taking it supplementally with a solid food source.

The PA to be included in the inventive composition may be prepared fromsoybeans, peanuts, wheat, oats, safflower, fish, milk, bovine liver,eggs, egg yolks, and other known sources of amino acids. The inventivecomposition may include nutritional supplements, such as protein, aminoacids, .alpha.-lipoic acids, .beta.-hydroxy-.beta.-methyl butyrate,glycine propyline-L-carnitine, carnitine, Russian tarragon, gymnemasylvestre, bitter melon, cissus quadruangularis, cinnamon and fenugreek,leucine peptide, leucine, isoleucine, valine, anacyclus pyrethrumextract, nettle root extract, CLA, tribulus, mulberry, ribose, caffeine,beta alanine, ZMA, betaine, L-aspartic acid, carnosine, and the like.

We expect that, as a supplement for typical healthy people seekingimproved muscle mass and strength, the inventive PA supplement ispreferably taken orally, either as a pill, capsule, powder, or liquiddrink type mix. In a hospital or medical setting for people with wastingdiseases or who are bedridden for long periods of time, we expect thatintravenous and/or other administration methods would be applicable aswell.

Phosphatidylcreatine is a prophetic composition based on the union ofthe known ergogenic aid creatine and our prophetic anabolic aidphosphatidic acid (PA). Creatine is used to boost intracellular ATPstores within muscle tissue, thereby increasing performance potential.There already exists a wealth of information regarding the benefit oforal phophatidylserine (PS) for performance and cortisol control, andoral phophatidylcholine (PC) for performance and cognitive enhancement.We expect phosphatidylcreatine to enable significant increases in musclemass and strength in mammalian users. One possible method of formulatingphosphatidylcreatine is in a slurry type mix similar to that describedin U.S. Pat. No. 6,399,661 to Golini concerning the manufacture of anoral creatine supplement. The creatine and phosphatidic acid areexpected to be provided in the ratio of about 5 to 3.Phosphatidylleucine is another prophetic composition based on a union ofPA and leucine which we expect to also prove to be an excellent anabolicaid. One possible method of formulating phosphatidylleucine is in aslurry type mix similar to that described above forphosphatidylcreatine. The leucine and phosphatidic acid are expected tobe provided in the ratio of about 5 to 3. The prophetic anticipatedamount of leucine to be provided is approximately 2-5 grams, morepreferably about 3 grams. Optionally, the method includes theadministration of leucine, isoleucine, and valine in a 2:1:1 ratio,e.g., 4 grams leucine, 2 grams isoleucine, and 2 grams valine.

The invention is not limited to the above description. For example,although it is preferred that PA be administered/ingested within theanabolic window following exercise, the inventive method alsocontemplates administering PA at other times of the day not tied to anexercise session. Similarly, while the preferred dosing is at least1.0-1.5 grams/day of PA, it is expected that more PA may be consumeddaily without adverse effects. Additionally, while the inventive methodand composition are chiefly targeted for human consumption, it iscontemplated to be used for/by any other mammals, e.g., horses, dogs,and the like. Dosing would likely be scalable by relative body weight ofthe mammal in question, e.g., horses may require is 10 to 40 grams, dogsmay require 0.1 to 3 grams, etc.

Having described certain embodiments of the invention, it should beunderstood that the invention is not limited to the above description orthe attached exemplary drawings. Rather, the scope of the invention isdefined by the claims appearing hereinbelow and includes any equivalentsthereof as would be appreciated by one of ordinary skill in the art.

What is claimed is:
 1. A method of increasing muscle mass and strengthin mammals, the method comprising the step of orally administering acomposition comprising a therapeutically effective amount ofphosphatidic acid.
 2. A method of increasing muscle mass and strength inmammals according to claim 2, wherein the mammal is human and thetherapeutically effective amount of phosphatidic acid is 0.5-4.0 gramsper day.
 3. A method of increasing muscle mass and strength in mammalsaccording to claim 2, wherein the therapeutically effective amount ofphosphatidic acid is approximately 1.0-1.5 grams per day.
 4. A method ofincreasing muscle mass and strength in mammals according to claim 2,said oral administration step further comprising the step of dividingthe therapeutically effective amount of phosphatidic acid into aplurality of doses per day with at least one dose being administeredwithin 1-2 hours following an exercise session.
 5. A method ofincreasing muscle mass and strength in mammals according to claim 2,wherein said oral administration step is executed to an exercisingsubject following exercise during the anabolic window.
 6. A method ofincreasing muscle mass and strength in mammals according to claim 5,further comprising the step of orally administering 20-100 grams ofprotein during the anabolic window.
 7. A method of increasing musclemass and strength in mammals according to claim 6, wherein the proteinis a complete protein containing all the essential amino acids.
 8. Amethod of increasing muscle mass and strength in mammals according toclaim 6, wherein the protein is whey or partially hydrolyzed collagenprotein.
 9. A method of increasing muscle mass and strength in mammalsaccording to claim 1, said composition further comprising atherapeutically effective amount of creatine.
 10. A method of increasingmuscle mass and strength in mammals according to claim 9, wherein saidtherapeutically effective amount of creatine is 3-20 grams.
 11. A methodof increasing muscle mass and strength in mammals according to claim 9,said composition including phosphatidylcreatine.
 12. A method ofincreasing muscle mass and strength in mammals according to claim 1,said composition further comprising a therapeutically effective amountof leucine.
 13. A method of increasing muscle mass and strength inmammals according to claim 12, wherein said therapeutically effectiveamount of leucine is 2-5 grams.
 14. A method of increasing muscle massand strength in mammals according to claim 12, said compositionincluding phosphatidylleucine.